Dementia is often assumed to be a disorder only of cognitive impairment, however, it is often accompanied by significant motor disability due in part to “paratonia”, a form of increased muscle tone. First observed by Dupre in 1910 (Dupre, E., Rev. Neurol. 1910; 20:54-56), it was characterized as “an inability to relax muscles in the setting of cognitive impairment”. Paratonia exerts its effects by increasing muscle resistance reflexively when a limb is moved passively, though can fluctuate in severity depending on level of relaxation. In advanced dementia, increased tone may also exist at rest and maintains muscle in a prolonged shortened state leading to fixed postures (contractures). Paratonia has been estimated to be present in 5% of those with mild cognitive impairments and 100% in those with advanced dementia (see, e.g., Hobbelen et al., Int. Psychoger. 2008, 20:840-852; Franssen et al., Arch. Neurol. 1993, 50:1029-1039; Souren et al., J. Geriatr. Psychiatry Neurol. 1997, 10:93-98; and Hobbelen et al., BMC Geriatr. 2007, 7:30).
Some of the consequences of fixed postures include difficulties in washing, dressing, feeding, and providing general care to a fully dependent person increasing caregiver burden. Contractures often lead to skin breakdown, infection, and pain upon movement, thereby reducing comfort and quality of life. Once contractures have developed, medical treatments are generally futile. However, contractures may be avoided or delayed, if paratonia is recognized and treated.
Botulinum toxins, in particular botulinum toxin type A, have been widely used to address hypertonic states such as dystonia, for example cranial dystonia (e.g., blepharospasm, oromandibular dystonia), cervical dystonia (e.g., spasmodic torticollis) and laryngeal dystonia (e.g., spasmodic dysphonia), and spasticity (e.g., post-stroke spasticity). Botulinum toxin is an exotoxin produced by the bacterium Clostridium botulinum that specifically binds to presynaptic cholinergic nerve terminals and inhibits the release of the neurotransmitter acetylcholine in a dose-dependent manner (Kao et al., Science 1976, 193:1256-1258). This results in local paralysis and hence relaxation of the muscles afflicted by the hypertonic state such as dystonia and spasticity. Injections of botulinum are generally well tolerated, have minimal side-effects, and are effective for approximately 3 months with peak effect occurring after about 4 to 6 weeks.
Currently, the main therapy for paratonia is the passive movement therapy (PMT), which aims to decrease high muscle tone and to sustain range of motion of the affected joints. However, there are general doubts about the beneficial effects of this widely used therapy. It was observed that the frail elderly patients, who often show signs of discomfort during the treatment, are prone to injury and not able to actively use regained mobility. In fact, a pilot study with PMT even showed an increased muscle tone in the PMT group, as compared to controls, indicating a possible association with muscle fibre injuries (Hobbelen et al., Nederlands Tijdschrift voor Fysiotherapie 2003, 113:132-137). A later multi-centre randomized controlled trial to assess the efficacy of PMT in dementia patients with paratonia showed that PMT has no beneficial effects on the muscle tone but shows a trend towards worsening of joint and limb stiffness compared with controls. PMT was therefore not recommended as an intervention in severe paratonia (Hobbelen et al., Int. Psychogeriatr. 2012, 24:834-844).
Thus, no effective treatment is currently available for patients afflicted with paratonia such that activities of daily living (ADLs) could be facilitated and discomfort and consequences of immobility could be delayed or prevented.